Acid‐sensing ion channels in neurones of the rat suprachiasmatic nucleus

We used reduced slice reparations to study ASIC‐like currents in the rat central clock suprachiasmatic nucleus (SCN). In reduced SCN preparations, a drop of extracellular pH evoked a desensitizing inward current to excite SCN neurones to fire at higher rates. Under voltage‐clamped conditions, all SCN neurones responded to a 5 s pH step to 6.4 with an inward current that decayed with an average time constant of 1.2 s to 10% of the peak at the end of step. The current was blocked by amiloride with an IC 50 of 14 μ m and was carried mainly by Na + , suggesting an origin of ASIC‐like channels. The SCN neurones were sensitive to neutral pH, with 94% of cells responding to pH 7.0 with an inward current. The study of sensitivity to pH between 7.0 and 4.4 revealed a two‐component dose‐dependent H + activation in most SCN neurones, with the first component (85% in amplitude) having a pH 50 of 6.6, and the second (15%) a pH 50 of 5. The ASIC‐like currents were potentiated by lactate and low Ca 2+ , but were inhibited by Zn 2+ . RT‐PCR analysis demonstrated the presence of mRNA for ASIC1a, 2a, 2b, and 3 in SCN. Compared to other central neurones, the unique presence of ASIC3 along with ASIC1a in SCN neurones may contribute to the high pH sensitivity and unusual inhibition by Zn 2+ . The high pH sensitivity suggests that the SCN neurones are susceptive to extracellular acidification of physiological origins and that the ASIC current might play a role in regulating SCN excitability.